biotech bulletin - bcil.nic.in · biotech bulletin is a bi-monthly publication ... cipla’s medpro...

Biotech Bulletin is a bi-monthly publication brought out by Biotech Consortium India Limited (BCIL), a company promoted by the Department of Biotechnology (DBT), Government of India and the All India Financial Institutions which is involved in facilitating accelerated development and commercialisation of biotechnology.

The bulletin is a useful compilation of latest clippings from newspapers, magazines and journals on relevant areas in biotechnology including healthcare, agriculture, market/collaborations, research and development.

The publication is brought out exclusively for our Biotech Club Members.

BioteCh Bulletin

editorial Board

Dr. Purnima Sharma,Managing Director

Vinod Kumar, Deputy ManagerLingeshwar B.S., Project Executive

Biotech Consortium india limited

5th Floor, Anuvrat Bhawan210, Deen Dayal Upadhyaya Marg,New Delhi – 110 002Tel: 011-2321 9064-67Fax: 011-2321 9063E-mail: [email protected]: http://www.bcil.nic.in

The articles have been reproduced as such from various sources and BCIL does not

authenticate the validity of the same.

CoNTENTSVol. XIV No. 2 ISSN No. 0972-737X Mar. - Apr.-2013

in the neWS

Milestones in curbing Malaria .......................................................................... 02

FDA approves new tuberculosis drug ........................................................... 02

India to scale up on TB Test that also detects drug resistance ............... 03

New Biotech Startegy paper soon with an eye on 2025 .......................... 04

Genomic Analysis: The Office Edition ........................................................... 05

Quality of Indian R&D in science is very high:IDRC .................................. 06

MARKet/CollABoRAtionS

Biocon net profit up 9% .................................................................................... 07

GSK, Biological E tie up for polio drug ......................................................... 07

Cipla’s Medpro deal largest in SA by Indian co ........................................... 08

Biosimilars to be $3.7b market globally by 2015 ........................................ 08

$10 billion-plus pharma deals set to return in 2013 .................................. 09

MeDiCAl BioteCh

Vaccine for Chikungunya virus ........................................................................ 10

Gold Nanoparticles could kill cancer without chemo ............................... 11

Designed Genomics ........................................................................................... 11

New Drug to figh Diabetes Developed ........................................................ 12

Potential Cure for AIDS Discovered ............................................................. 13

AGRi BioteCh

Maharashtra formulates special policy for organic farming ...................... 14

Genome feat hope for chhole, pakora aficionados .................................... 15

GM tobacco plant can treat rabies ................................................................. 15

Golden age of GM Crops ................................................................................. 16

Rice, a silver bullet to fight off cancer ........................................................... 18

Scientists discover genetic key to more efficient crops ............................ 18

R&D iDeAS

Fish stem cells may restore human vision .................................................... 19

New TB drug ready for clinical trial .............................................................. 19

IISc Scientists Discover new molecule for cancer ...................................... 20

Bacteria that can cure ....................................................................................... 22

Modified Virus kills liver cancer cells ............................................................. 22

Cells with promise ............................................................................................. 23

March - April 20132

FDA approves new tuberculosis drug

Milestone in curbing malaria

MINT2 January, 2013

A study in September in The Lancet found that almost 44% of patients with tuberculosis in countries such as Russia, Peru and Thailand showed resistance to at least one second-line drug, or a medicine used after another drug has already failed.

Treating drug-resistant tuberculosis can take years and can cost 200 times as much as treating the ordinary form of the disease.

“This is quite a milestone in the story of therapy for TB,” Paul Stoffels, the chief scientific officer at Johnson & Johnson,

MILLENNIUM PoST16 March, 2013

Scientists at the International Center for Genetic Engineering and Biotechnology (ICGEB) in New Delhi deserve to be congratulated for having discovered antigens from which a malaria vaccine can be developed. This discovery will lead to the elimination of this dangerous disease in the long run. Malaria remains a disease that has not yet been conquered by humanity and continues to take its toll yearly despite advances in science. It continues to be a scourge of humanity, especially in tropical and semi-tropical countries, in spite of all the efforts to control it. The scientists in New Delhi has thus done humanity a signal service as their

ThE DRUG, To BE CALLED SIRTURo, IS ThE FIRST IN A NEW CLASS oF DRUGS ThAT AIMS To TREAT TB’S DRUG RESISTANT STRAIN

said in an interview.he said the approval marked the

first time in 40 years that the agency had approved a drug that attacks tuberculosis in a different way than the current treatments on the market. Sirturo works by inhibiting an enzyme needed by the tuberculosis bacteria to replicate and spread throughout the body.

Sirturo, also known as bedaquiline, would be used on top of the standard treatment, which is a combination of several drugs. Patients with drugresistant tuberculosis often must be treated for 18 to 24 months.

Even as it announced the approval, however, the FDA also issued some

work brings the dream of a preventive vaccine against malaria a step closer. The scientists have tested a large number of antibody combinations which inhibit the invasion of the Plasmodium falciparum, a dangerous strain of the parasite that causes malaria and brings about deaths. Their study identifies key parasite antigens that can form the basis of an effective malaria vaccine, with the next step being to devise a strategy to deliver these antigens into the human body in such a way that they elicit an immune response. Thus an approach has been developed that effectively blocks the malaria parasite and leads to its neutralisation.

This is important as malaria is one of the important vector-borne diseases in India that cause illness and death.

words of caution.“Multidrug-resistant tuberculosis

poses a serious health threat throughout the world, and Sirturo provides muchneeded treatment for patients who have don’t have other therapeutic options available,” Edward Cox, director of the office of antimicrobial products in the FDA’s center for drug evaluation and research, said in a statement. “however, because the drug also carries some significant risks, doctors should make sure they use it appropriately and only in patients who don’t have other treatment options.”

The consumer advocacy group Public Citizen opposed approval in a letter to the FDA in mid-December, saying that the results of a limited clinical trial showed that patients using bedaquiline were five times as likely to die than those on the standard drug regimen to treat the disease.

“Given that bedaquiline belongs to an entirely new class of drugs, it is entirely feasible that death in some cases was

on an average, 40,297 Indians die of this mosquito-borne disease every year with the overall number of malaria cases being approximately 9.75 million. A Lancet study published in 2011 indicated that malaria actually killed an estimated 46,800 Indians in 2010. The study estimated 4,800 malaria deaths in children younger than 5 years and 42,000 malaria deaths in those aged 5 years or older for 2010 as against 19,000 malaria deaths in children younger than 5 years and 87,000 malaria deaths in those aged five years or older in 2002. These are huge losses to the disease. According to the World Malaria Report 2011, over 70 per cent of India’s population faces the risk of malaria infection with around 31 crore people facing the highest risk. India has over 10 crore suspected malaria cases but only 15.9 lakh could be confirmed in 2010. It is to be hoped that the efforts of the scientific team will continue to bear fruit and provide a much needed cure to millions suffering from the disease.

BULLETINBiotech

March - April 2013 3

due to some unmeasured toxicity of the drug,” the letter said.

Sirturo carries a so-called black box warning alerting patients and healthcare professionals that the drug can affect the heart’s electrical activity, which could lead to an abnormal and potentially fatal heart rhythm. The warning also notes deaths in patients treated with Sirturo. Nine patients who received Sirturo died compared with two patients who received a placebo. Five of the deaths in the Sirturo group and all of the deaths in the placebo arm seemed to be related to tuberculosis, but no consistent reason for the deaths in the remaining Sirturo-treated patients could be identified.

Doctors Without Borders and the Bill and Melinda Gates Foundation, both active in the fight against tuberculosis and other global diseases, applauded the

FDA’s decision.Jan Gheuens, interim director of the

TB programme for the Gates Foundation, called it a “long-awaited event” and said the fight against TB had not benefited from new drugs in the way hIV had. Beyond the benefits of the drug itself, he said the quick approval process could be a model for other drugs in dire need in the developing world.

he also suggested, however, that more trials should be conducted to get a better understanding of the side effects that led to the black box warning.

The FDA approved bedaquiline under an accelerated programme that allows the agency to conditionally approve drugs that are viewed as filling unmet medical needs with less than the usual evidence that they work. The drug’s approval was based on studies that showed it killed bacteria more quickly

than a control group taking the standard regimen, but it did not measure whether in the end patients actually fared better on bedaquiline. Johnson & Johnson will conduct larger clinical trials to investigate whether the drug performs as predicted.

In a statement responding to Public Citizen’s letter, a spokeswoman for Johnson & Johnson said the company is committed to supporting appropriate use of Sirturo and would “work to ensure Sirturo is used only where treatment alternatives are not available”.

Stoffels said the hope is that other new tuberculosis drugs will also be approved that, when used in combination with bedaquiline, could shorten and simplify the current standard of treatment.

“That is still a long time away,” he said, but “this is a first step in a new regimen for TB”.

India to scale up on TB test that also detects drug resistanceBUSINESS LINE2 February, 2013

A test that detects tuberculosis and shows whether a patient is resistant to a key tuberculosis drug is set to find greater use in India’s TB control programme.

The Xpert test, endorsed by the World health organisation, detects TB accurately and in two hours, besides simultaneously showing whether the patient is resistant to rifampicin, as an indicator of multidrug resistance.

The Government TB-contro l programme already uses about 30 machines, and will add another 40 this year, a Union Health Ministry official told Business Line. With a handful of new tests in the pipeline, the Government is

staggering its approach and not putting all its eggs in one basket, the official added.

At present, the programme that covers thecountry is a mix of conventional tests (liquid and solid), line probe assays

and the Xpert test. The time for diagnosis also varies across these tests, from a month, to a day to a couple of hours, respectively, and the machines and kits arc accordingly placed at primary healthcare centres, regular hospitals or large tertiary hospitals, the official said.

neGotiAteD PRiCeA recent review on The Xpert

test published by The Cochrane Library also gave the test its thumbs-up. The test is more sensitive than sputum smears and is less operator-dependent, said Dr Madhukar Pai, Associate Professor

CuRBinG tBv The Xpert test is made by US company, Cepheid.

v In August 2012, international donors provided funding to reduce the cost of Xpert cartridges from $16.86 to $9.98.

v The reduced price is available for the public sector in 145 high-burden and developing countries.

v With about two million annual TB cases, and nearly 750 deaths per day — India accounts for one-fifth of the global prevalence.

March - April 20134

(Department of Epidemiologv and Biostatistics) with McGilf University, Canada.

“While thousands of TB bacteria must be present in each millilitre of sputum sample for TB to be detected under the microscope, Xpert can detect TB bacteria at much lower concentrat ions . In addit ion, the conventional microscopy approach does not detect drug resistance, while Xpert can rapidly detect resistance to rifampicin, the most important first-line

TB drug,” explained Dr Pai, one of the authors of the recent study.

The kits would be available for the public sector at S10 per cartridge, he said. It is available in the private sector, but priced very high (as much as Rs 3,000 or higher per test), he said, adding efforts were underway to it more affordable in the private sector.

The Government gets the machine and kit at the mentioned negotiated price, the Ministry official concurred, adding that for patients at Government

institutions, the test were free.The private sector is excluded from

this subsidised pricing and this should be changed, said Dr Pai, especially since poor patients in India visit private hospitals, as well, he said.

The recent review, the author said, was since there were few studies on the test when the Who approved it. The latest review combines results from 18 studies and provides greater confidence in the early results that were used by Who for the policy, he added.

New biotech strategy paper soon with an eye on 2025

ThE hINDU5 February, 2013

The Union Government’s Department of Biotechnology will come out with a ‘Biotech Strategy 2013 paper’ in April this year aimed at bringing together the Government, industry, research institutions and global organisations.

The strategy is aimed at helping Indian biotech and healthcare sectors achieve revenues of $ 100 billion by 2025, said K. Vijay Raghavan, Secretary of the Department, delivering the keynote address at the Bangalore India Bio 2013 here on Monday.

CRuCiAl MoMenthe said the country is on the

threshold of key global developments and therefore the Government and industry would play crucial roles. Since India has an abundance of technical manpower, there was need for strategies to harness the wealth,

AIMS To BRING STAKEhoLDERS ToGEThER To AChIEVETARGET GRoWTh

he said.Mr. Raghavan said the Department

is in the final stages of reviewing the strategy.

he said the paper would also look at how to increase collaborations to support basic research. Also, the Department’s support to basic re-search would continue to bring in the right

linkages, he said.Inaugurating the event, Chief

Minister Jagadish Shettar said the IT capital of India has truly emerged as the science capital, thanks particularly to the biotech sector. He said the first biotechnology policy was unveiled in Karnataka in 2001.

While Karnataka is home to about 52 per cent of core biotech companies in the country, 26 per cent of biotech export revenues are generated from here, Mr. Shettar said.

having achieved the objectives to a large extent, the policy was modified in 2009 through the Millennium Biotech Policy version, he said.

The revised policy, besides offering fiscal incentives, also aims at placing necessary infrastructure for biotech parks and has received encouraging

A world-class incubation centre and common instru-mentation facility is coming up there, he said. Karnataka Chief Minister Jagadish Shettar being greeted by K. Vijay Raghavan, Secretary. Central Department of Biotechnology, and S. V. Ranganath. State Chief Secretary, while Anne MacColL CEo, Scottish Development International. Minister for Water Resources Basavaraj Bommai and Biocon Chairperson & Managing Director Kiran Mazumdar-Shaw look on during the inauguration of Bangalore India Bio 2013 on Monday.

BULLETINBiotech


ThE TASK oF SEQUENCING ThE hUMAN GENoME AND KEEPING ThAT hIGhLY PERSoNAL INFoRMATIoN SECURE REMAINS AN ARDUoUS

oNE, BUT A NEW DEVICE IS ALL SET To REVoLUTIoNISE ThE REACh oF GENoMIC MEDICINE

response from the industry.he also said the regulatory

mechanisms will have to be revisited if the combined turnover of Indian biotechnology and healthcare sectors has to touch $ 100 billion by 2025.

Mr. Shettar quoted from the report of the Association of Biotechnology-Led Enterprises (ABLE) — ‘Indian

biotechnology: The road map to the next decade and beyond’.

He said 12 biotechnology finishing schools sanct ioned by the State Government are doing well and have received encouraging feedback from the industry and academia. Appreciating this model, the Central Government has sanctioned fellowships of Rs. 5,000 per

student per month for three years.Mr. Shettar said establishing a state-

of-the-art biotech park in Bangalore is finally taking shape with Alexandria Real Estate starting Alexandria Knowledge Park in Ban-galore helix.

A world-class incubation centre and common instrumentation facility is coming up there, he said.

Genomic analysis the office edition

FINANCIAL ChRoNICLE5 February, 2013

The price of sequencing a person’s genome - putting in order all three billion base pairs of DNA in a set of human chromosomes — keeps dropping. Bui Interpreting the billions of letters in a prison’s DNA blueprint for use in medicine, and keeping that highly personal information secure and anonymous, is still a complex task.

over the just few years, the cost of mapping one person’s genome has dropped to around $6,000 from about $250,000, and it is expected to go far lower. And as genomic medicine quickly evolves, a powerful computer packed with software has arrived to interpret sequences privately within the walls of a lab, in contrast to systems that use the internet and distant servers. The software parses variants in DNA looking for ones that may lie important.

The appliance, made by a human-genome interpretation company called Knome, is the size of .1 tile cabinet and costs $I25.000 Knome will begin shipping it in coming months to researchers investigating the genetic basis for cancer,

rare diseases and drug response, said Jorge Conde. a co-founder of the company along with George M Church, a geneticist and professor at harvard Medical School.

For an additional, annual fee of $25,000, users can buy technical support and regular updates of the software for the machine, called the knoSYSTM100.

Because people can he identified by genetic data posted online, the privacy offered by the appliance, and its ability to discretely analyse data directly in a lab or office, may be an advantage. Lee Watkins Jr. director of bioinformatics at the Center for Inherited Disease Research at Johns hopkins University is considering buying one, in part for that reason. “You have control over it physically within your walls and logically within your network.” he said. “Everyone’s DNA is a very personal thing.”

Peter I Nagy, a director of the personalised genomic medicine laboratory at Columbia University, is considering ordering a Knome machine for use in a clinical setting. Such machines may broaden the reach of genomic medicine, particularly in smaller labs.

“Normally you need a slew of people to maintain a centre to process this

data.” said Nagy, who is also an assistant professor of pathology and cell biology. “Basically this machine removes the need to maintain an expensive computational facility and a group of people’ who make sure the operating system is working and keep the reference data up to date.” And the appliance doesn’t tax internet connections, he added.

The machine takes raw data from sequencers at Il lumina, Complete Genomics and other DNA sequencing companies, which can be downloaded onto a hard disk. Then the machine’s software analyses the data, selecting a list of potentially noteworthy items.

If he had the machine, Nagy said, he

March - April 20136

would go carefully through this list. “We have to validate the items, confirming or rejecting the interpretations,” he said. he would use the machine for cancer genetics, looking for specific disruptions that are driving a tumor, and in evaluating diseases that run in families.

Michael Schetz, an assistant professor at Cold Spring harbor Laboratory on Long Island, said appliances like Knome’s weren’t needed at his lab “We have large dusters of equipment so that we can do analysis on site,” he said. “But a smaller institution might find value in a pre-configured unit that’s alive and ready to go.” so long as there is someone at the company to answer questions and offer technical support.

The machine tackles a tedious,

intensive task, searching for points of difference between a person’s genome and the standard, or “reference.” genome. “There may be hundreds of thousands of variants — or far more — that we find in the person that are different from the reference genuine.” Watkins ol Johns hopkins said

The machine’s algorithms examine these d i f ferences based on the investigator’s search criteria, looking for medically relevant ones. “You might filter down to the variants that matter for mutations known to be causative or associated with a disease.” Conde of Knome said. Programs might also compare children’s genomes to those of their parents, searching for a genetic cause of rare or inherited diseases.

Stephen Liggett, Director of the Centre for Personalised Medicine and Genomics at the University of South Florida, has ordered a machine from Knome. “When you would like to get genetic information quickly interpreted, and take it to the patient,” he said, “this machine is right there” in help

Eric Topol, a professor of genomics at the Scripps Research Institute in La Jolla, California, and author of The creative destruction of medicine, cautioned that appliances like Knome’s would still require personnel steeped In molecular biology and genetics to sift through and evaluate its findings.

“It’s not for your neighborhood doctor just yet.” he said, “although that time will come.”.

Quality of Indian R&D in science very high: IDRC

FINANCIAL ChRoNICLE12 February 2013

Canada-based International Develop-ment Research Centre has chosen India for its research in agriculture and allied areas as the quality of research and science in the country is very high, a top official of the agency said on Monday.

The quality of research and science in India is very high and that is why IDRC has chosen the country for its research

in agriculture, water and climate change, besides waste management, IDRC president David M Malone told PTI.

IDRC is spending nearly $260 million on various countries for research in agriculture and health sector, he said, adding India is being given $30 million for research projects, mainly in the agriculture sector, through Tamil Nadu Agricultural University (TNAU) here.

on the ongoing projects in TNAU, Malone said IDRC is funding two projects

one on ‘enhancing preservation of fruits in South India, under Canadian International Food Security Research Funds programme, which involves University of Guelph, Canada, TNAU and International Technology Institute, Sri Lanka and an NGo, MYRADA, with an outlay of Rs 4.99 crore.

Another Rs 1.47 crore project is on ‘revalorising small millets enhancing the food and nutritional security of women and children in rain-fed regions of South Asia using underutilised species, he said.

Canada also provides funds for research in health sector in India, he said. on pulses, he said Canada, despite being the largest exporter of pulses to India, will be delighted to see india enhance production.

“We will be delighted to see India enhancing its production, this would lead to food security globally and the international market will flood with pulses,” he said.

“IDRC IS SPENDING NEARLY $260M oN VARIoUS NATIoNS FoR RESEARCh IN AGRICULTURE AND hEALTh” DAVID M MALoNE PRESIDENT, IDRC

BULLETINBiotech


FINANCIAL ChRoNICLE29 January 2013

DRUG major GlaxoSmithKline and hyderabad-based Biological E will set up a joint venture to develop a six-inone vaccine for polio and other infectious diseases.

GSK and Biological E have inked a pact to form a 50:50 joint venture for the early stage research and development of a six-in-one combination vaccine to protect

children in India and other developing countries from polio and other infectious diseases, the two companies said in a statement.

Completion of the transaction is expected in 2013, subject to several

conditions including regulatory approval of the joint venture (JV), the statement added.

“If approved, the vaccine, which would combine GSK’s injectable polio vaccine and Biological E’s pentavalent

GSK, Bio-logical E tie up for polio drug

vaccine for diphtheria, tetanus, whooping cough (whole cell pertussis), hepatitis B, and haemophilus influenza type B, could be the first of its kind,” the statement said.

The JV will bear the development costs for the candidate vaccine, which is expected to enter phase I development in the next two years, it added.

“A very small initial cash investment will be made by both companies to cover start-up costs for the JV and subsequent development costs will be split equally,” it said.

The vaccine would enable fewer injections for children thereby improving compliance in immunisation schedules, the statement added.

BUSINESS STANDARD26 January 2013

Bangalore-based biotechnology major Biocon witnessed a nine per cent increase in its net profit at Rs 92 crore during the quarter ended December 31, on Rs 84 crore for the corresponding quarter last year. The company attributed the growth to volume expansions, price increases and improved export realisations.

Total revenues for the october-December period were Rs 643 crore, an increase of 24 per cent y-oy. operating earnings were Rs 167 crore, up 25 per cent.

Kiran Mazumdar-Shaw, CMD, Biocon said: “We saw a combination of volume expansions, price increases and improved export realizations. We have performed well across all our business verticals. We continue to gain market share for Biosimilar Insulins in which now accounts for a significant part of our business.”

The company also said that during the third quarter the biopharma business

witnessed a yoy growth of 22 per cent led by an improved product mix. Small Molecules sales to US and Europe remain robust and emerging markets delivered strong sales in Insulins and immunosuppressants.

“We have signed an option agreement with Bristol Myers Squibb ( BMS) for the global clinical development of our oral Insulin program: IN-105. This alliance with BMS is a strategic partnership which will help us undertake targeted global trials under a US IND. BMS has the right to exercise an option for exclusive worldwide license post the completion of these trials,” added Ms Shaw.

The company’s branded formulations business delivered a growth of 35 per cent during the nine month period.

Biocon net profit up 9%

Biocon also introduced several new products in the quarter across cardiology, immunology and comprehensive care.

“our research services arm continues to grow robustly, delivering 34 per cent YoY growth for the nine month period. We expect the recent partnership with GE to leverage novel platform technologies, thereby creating further value differentiators,” the company said.

Going forward the company aims to have higher contribution from biosimilars, research services and branded formulations to the overall revenue. The company has also indicated that it intends to touch a topline of $700 million by Fy15 from the current $450 million.

Biocon stock gained 1.6 per cent and closed at Rs 267.55 per share on NSE.

March - April 20138

Cipla’s Medpro deal largest in SA by Indian coDNA2 March 2013

With its offer to buy Cipla Medpro, drugmaker Cipla is slated to get a strong foothold in the South African market, and later on into neighbouring markets.

on Thursday, the Mumbai based drugmaker announced that it had made an all-share offer of $508.6 million to acquire 100% of Medpro. This offer follows an earlier offer made in November to buy about 51% of Medpro for $220 million.

Experts say Cipla might have reasoned out to pay $508.6 million or 10 rand per share in order to prevent the deal from falling out. In 2012, Cipla had offered to buy majority stake in Medpro at 8.55 rand per share. however, Medpro’s shares appreciated since the proposed offer. There was speculation that if Cipla did not hike its offer, the deal can fall apart.

“A few weeks ago, there was intense speculation that the deal might collapse owing to the recent appreciation of Medpro’s shares and Cipla’s initial offer price. Cipla surely is not wanting to let go of this key market,” said an analyst.

Cipla’s CEo Subhanu Saxena said South Africa is a key market and the company expects demand for generic drugs in that market to grow by about 14% per year.

Estimates by GBI Research, an intelligence firm state that the market for pharmaceuticals in South Africa was $3.8 billion in 2011, and is expected to reach $7 billion in five years time.

This deal is arguably the biggest by an

Indian drugmaker in the South African market. A few years earlier, Lupin had acquired a South African firm called Pharma Dynamics for a considerably smaller amount.

According to Ranjit Kapadia, senior vice president, Centrum Broking, this deal can help Cipla enhance their presence in other markets in Africa like Nigeria, Tanzania, etc. “After buying 100%, they will then de-list the firm from the Johannesburg stock market.”

Medpro currently distributes Cipla’s products in South Africa. Cipla Medpro said the deal is dependent on regulatory and board approval. It needs 75% shareholder approval for the deal to go through.

Biological E chairman Vijay Kumar Datla said that the company expects to leverage the partnership to accelerate the development of the hexavalent vaccine

and make IPV accessible for developing countries in the post eradication phase for polio.

“The partnership reinforces the

commitment of both companies to support the World health organisation’s global polio eradication programme,” the statement said.


ThE global market for biosimilars is expected to grow to $3.7 billion

by 2015, the key driver will be the impending patent cliff and the rush of pharma companies for development and collaborations, according to a study report by consulting firm Grant

Biosimilars to be $3.7b market globally by 2015

Thornton.of the total deals, 40 per cent of

them originate in the US, which also continues to lead in terms of the development potential with 45 per cent share of all targeted alliances, followed by Europe at 18 per cent, India at 12 per cent, Japan and South Korea both also at 12 per cent, the report said.

It is estimated that between

BULLETINBiotech


FINANCIAL ChRoNICLE8 January, 2013

Get ready for the return of the $10 billion-plus drug deal.

Pharmaceutical companies including Pfizer and Bristol-Myers Squibb have spent the last several years digesting earlier acquisitions, refocusing their product development and setting aside cash in anticipation of expiring patents. Now, the expectation is they’re ready to start buying again. Led by Pfizer and Merck, five of the largest US drugmakers had more than $70 billion in cash, near cash and shortterm investments at the

end of the third quarter.“We’re through many costcutting

programmes, restructur ings and portfolio arrangements,” said henry Gosebruch, managing director of healthcare mergers and acquisitions at JP Morgan Chase. “When you put that together with record levels of cash available and improving, but still moderate R&D productivity, we think there will be more big pharma M&A activity in 2013.“

Johnson & Johnson, Abbott Labora-tories, Sanofi, Pfizer and Merck have already shown interest in one purchase that may top $10 billion: Bausch & Lomb,

$10 billion-plus pharma deals set to return in 2013

MEG TIRRELL, JEFFREY MCCRAC-KEN & DREW ARMSTRoNG

2009 and 2019, 21 biologics with a market value of over $50 billion will lose patent protection in the US alone, further creating opportunity. The biosimilar journey had begun in 2009, with a key alliance of five powerful players and later the spate of such collaborations continued in the next three years with 17 alliances in 2010, 12 in 2011 and 15 in 2012. While 30 per cent of the alliances were structured as acquisitions, rest were collaborative agreements for development, l icensing and marketing.

“While regulators are in the process of framing policies and guidance across the globe, the industry is facing several challenges such as product differentiation, meeting requirements for inter-changeability, increasing cost of good manufacturing practices, requirements on facility and manufacturing as compared to traditional drugs,“ says the report.

Area of focus Between 2009 and 2019, 21 biologics

with a value of $50b will lose patent in the US alone

For Dr Reddy’s, global biosimilor sole in 2012 stood at $ 26m, growing 45 per cent over 2011

Cipla hopes to develop bio-similars for Roche’s Avastin and herceptin and Amgen’s Enbrel

For Dr Reddy’s, global biosimilar sale in 2012 stood at $26 million, growing 45 per cent over 2011, while Ranbaxy expects to launch three biosimilars in 2015 and has development agreements with Biovel Lifescienes and Plenex. Cipla hopes to develop biosimilars for Roche’s Avastin and herceptin and Amgen’s Enbrel.

But despite the inherent challenges, manufacturing and treatment costs are less than that of innovator products.

Back home, Intas Pharma has launched five biogeneric products and has eight biosimilars and monoclonal antibodies in the pipeline. Also, Emcure has a manufacturing contract with Roche for biologic drugs such as herceptin and Mabthera.

March - April 201310

Vaccine for Cikungunya virusDECCAN hERALD23 February 2013

Researchers from the Emerging viruses Department in Marseille, France in collaboration with the University of Sydney demonstrated that the engineered viruses exhibit a stable phenotype with a significantly decreased viral fitness or replication capacity, making it a new vaccine candidate for this emerging viral disease.

There is an immense need for the development of vaccines targeting many emerging viral pathogens. ChIKV has been responsible for several million human cases over the last decade and represents a striking example of a re-emerging, arthropod-borne, human pathogen for which no licensed vaccine exists.

Worryingly, one of the vectors of ChIKV, the mosquito Aedes albopictus, has dispersed into new regions - including temperate areas

- resulting in outbreaks of this disease where they had never been previously observed, for example in Italy.

Using the large-scale codon re-encoding method, Antoine Nougairede and colleagues were able to synthetically modify the nucleic acid composition of the virus without modifying the encoded viral proteins.

When this method was applied to poliovirus and Influenza A virus, it resulted in a live but attenuated virus that had significant reduction of viral fitness.

In contrast with previous studies, which employed a targeted approach of codon re-encoding, this new study demonstrates that a random approach reduced the replicative fitness of CHIKV in both primate and arthropod cells.

The employed strategy also prevented the reversion of the attenuated phenotype

by mutation or recombination, thus reducing the possibility that the newly created virus strain could evolve back to the pathogenic version.

The findings suggest that large-scale codon re-encoding can provide a strong basis for the rapid design of next-generation viral vaccines against emerging viral pathogens, as soon as their genome sequence has been determined, according to the study published in the journal, PLoS Pathogens.

It represents an exciting route to vaccine development because it intrinsically alleviates the likelihood of novel pathogenic properties of the designed live vaccine, and allows modulation of the amount of reduced fitness by altering the terms and degree of the genetic re-encoding.

the eye-care company, is for sale by Warburg Pincus.

The private equity firm is seeking at least $10 billion for the business and those companies may be bidders, according to people with knowledge of the matter.

Big drugmakers will probably be on the hunt for assets to fill revenue holes left by expired patents. Pfizer’s Lipitor, which drew more than $12 billion in

annual revenue at its peak, lost marketing exclusivity in November 2011. Eli Lilly lost patent protection on its top-seller, the antipsychotic Zyprexa, in october 2011. The drug had drawn more than $5 billion in peak sales. New York-based Bristol-Myers faced generic competition last year to Plavix, its bestseller with more than $7 billion in revenue.

At the same time, they’ve got deep pockets. Pfizer ended the third quarter

with $23 billion in cash, near cash and short-term investments. Lilly had $6.9 billion, while Merck had $18.1 billion, and J&J, $19.8 billion.

“Many large cap pharma companies still face a patent cliff and have the financial capability and strategic willingness to partner and acquire their way to continued innovation,” Leerink Swann analysts including Seamus Fernandez wrote in a January 3 report.

BULLETINBiotech


Designed genomics


The deliberate modification of the genome is known as designed genomics. It involves targeted, specific modification of the genetic information of living organisms. The technologies that were earlier

developed for the insertion of a gene into a living cell were found to have certain limitations. Apart from reproducibility, random nature of the insertion of the new sequence into the genome and blind positioning of the new gene that may disturb the functioning of other genes were a few limitations. They could also

trigger the process of ‘cancerisation’. The major advantage of designed genomics is precision and reproducibility.

Due to the recent developments in the area of genome engineering, it is now possible to enhance the de novo assemblies of DNA at a reduced cost. “These developments promise genetic engineering with unprecedented levels of design originality and offer new avenues to expand

both our understanding of the biological world, and the diversity of applications for societal benefit”, write P A Carr and G M Church of MIT’s Media Lab.

Designed genomics, a very active

ThE TEChNoLoGY hAS A WIDE RANGE oF PoSSIBLE APPLICATIoNS, LIKE CoRRECTIoN oF GENES CARRYING hARMFUL MUTATIoN,

PRoDUCTIoN oF ThERAPEUTIC PRoTEINS & DEVELoPMENT oF NEW GENERATIoNS oF GENETICALLY MoDIFIED PLANTS

Gold nanoparticles could kill cancer without chemoMUMBAI MIRRoR23 January 2013

how do you annihilate lymphoma without using any drugs? Starve it to death by depriving it of what appears to be a favorite food: hDL cholesterol.

Northwestern Medicine researchers discovered this with a new nanoparticle that acts like a secret doubleagent. It appears to the cancerous lymphoma cell like a preferred meal - natural hDL. But when the particle engages the cell, it actually plugs it up and blocks cholesterol from entering. Deprived of an essential nutrient, the cell eventually dies.

A new study by Shad Thaxton and Leo Gordon shows that synthetic hDL nanoparticles killed B-cell lymphoma, the most common form of the disease, in cultured human cells, and inhibited human B-cell lymphoma tumour growth in mice.

“This has the potential to eventually become a nontoxic treatment for B-cell

lymphoma which does not involve chemotherapy,” said Gordon, a co-corresponding author. “It’s an exciting preliminary finding.”

Recent studies have shown that B-cell lymphoma is dependent on the uptake of natural hDL-short for high-density lipoprotein - from which it derives fat content, such as cholesterol.

The nanoparticle-originally developed by Thaxton as a possible therapy for heart disease - closely mimics the size, shape and surface chemistry of natural hDL particles.

But it has one key difference: a five nanometer gold particle at its core.

Thus, when the nanoparticle is incubated with human B-cell lvmphoma cells or used to treat a mouse with the human tumour, it socks lymphoma with a double whammy.

After it attaches to the lymphoma cell, the gold particle’s spongy surface sucks out its cholesterol while the gold core prevents the cell from absorbing

more cholesterol typically carried in the core of natural hDL particles.

The researchers used gold nano-particles as it can be made in a discreet size and shape; they are excellent scaffolds for creating synthetic hDLs that closely mimic those found in nature.

“Like every new drug candidate, the hDL nanoparticle will need to undergo further testing,” Shad Thaxton noted.


field of research at present, involves introducing a gene into a chromosome to obtain a new function. The insertion of gene is also to compensate for a defective gene, particularly by making it possible to manufacture a functional protein if the protein produced by the patient is defective.

Designed genomics also involves inactivation or ‘knock-out’. The purpose of inactivation or ‘knock-out’ is to know the function of a gene by observing the anomalies that occur as a result of its inactivation.

Correction aims to remove and replace a defective gene sequence with a functional sequence. Another aspect of designed genomics is ‘correction’. It is intended to correct short sequences (sometimes just a few nucleotides), such as in the case of sickle cell anaemia.

Designed genomics, a technology based on gene targeting, has a wide range of possible applications, like the correction of a gene carrying a harmful mutation, the production of therapeutic proteins and the development of new generations of genetically modified plants.

Gene targeting technology can bring precise changes into the protein coding part of a gene if one knows the mutation that causes the disease.

The use of gene targeting to evaluate

the function of genes in the living mouse is now a routine procedure. A mouse could also be used to produce a human version of protein. We now know that more than 90 per cent of the genes have a function shared between a mouse and a man. More than 10,000 genes have been targeted in mice. More than 500 different models of human diseases, including models for hypertension, atherosclerosis, cancer, diabetes and cystic fibrosis have been produced by gene targeting. Gene targeting has also been used to understand the role of individual genes in embryonic development, adult physiology and aging.

Mario Capecchi of the University of Utah, Martin Evans of the Cardiff

University and oliver Smithies of the University of North Carolina at Chapel hill have been jointly awarded the Nobel Prize in Physiology or Medicine for their discoveries of “principles for introducing specific gene modifications in mice by the use of embryonic stem cells.“ Capecchi demonstrated that defective genes could be repaired by homologous recombination with the incoming DNA. homologous recombination is a type of genetic recombination in which nucleotide sequences are exchanged between two similar or identical molecules of DNA. Capecchi discovered genes crucial for mammalian organ development and the

body plan in general. Capecchi’s research has shed light on the causes of several birth defects. Evans discovered that chromosomally normal cell cultures could be established directly from early mouse embryos, referred to as embryonic stem (ES) cells, and developed mouse models for human diseases. Smithies discovered that all genes may be accessible to modification by homologous recombination. Smithies used gene targeting to develop mouse models for inherited diseases such as cystic fibrosis and the blood disease thalassemia. he also developed numerous mouse models for common human diseases such as hypertension and atherosclerosis.

Creating designed genomic modifi-cations has three major advantages for introducing mutations into mice, writes Capechchi. The investigator can choose which genetic locus to mutate. The technique takes full advantage of all the resources provided by the known sequences of the mouse and human genomes. The investigator has complete control of how to modulate the chosen genetic locus. Gene targeting in mice has pervaded all fields of biomedicine, and as Capechchi concludes “The repertoire of biological phenomena that can be studied through the use of gene targeting is only limited by the imagination of the investigator.”

New Drug To Fight Diabetes DevelopedThE STATESMAN5 March 2013

Scientists have developed a simple once-a-day jab for diabetes that lasts 40 hours compared to insulin injections that remain effective only for 18 hours.

Many pat ients have to in ject themselves with insulin several times a day in order to keep their blood sugar level steady.

however, the new drug, Tresiba, now

available in the UK, makes it easier to keep diabetes under control as it lasts 40 hours instead of a maximum of 18 hours and is much more stable.

If patients happen to miss an injection because of the demands of their busy lives they are less likely to suffer the potentially fatal low blood sugar “crash” called hypoglycaemic shock, ‘Express.co.uk’ reported.

Doctors have hai led the new treatment which can be used to manage

both Type 1 and Type 2 diabetes.“Many of my patients tell me they

have difficulty taking their insulin at exactly the same time each day. This is often for reasons which we can all sympathise with,” Melanie Davies, Professor of Diabetes Medicine at the University of Leicester, said.

“We might get stuck in traffic picking the children up from school or our shifts at work might change,” said Prof Davies.

“Now for the first time insulin-dependent diabetes patients will have the peace of mind that their blood sugar is still under control if they are, on occasion, not able to take their insulin dose at the same time each day,” Prof Davies said.

BULLETINBiotech


Potential cure for AIDS discovered

MUMBAI MIRRoR17 January 2013

An Australian scientist said Wednesday he had discovered how to turn the hIV virus against itself to stop it progressing to AIDS, describing it asa major break through in finding a cure for the disease.

David harrich, from the Queensland Institute of Medical Research, said he had successfully modified a protein in hIV that the virus needed to replicate and instead made it “potently” inhibit virus growth.

“I have never seen anything like it. The modified protein works every time,” said harrich.

“If this research continues down its strong path, and bear in mind there are many hurdles to clear, we’re looking at a cure for AIDS.”

Harrich said the modified protein, which he had named Nullbasic, had shown a “remarkable” ability to arrest hIV growth in a lab environment and could have exciting implications both in curbing AIDS and treating existing hIV sufferers.

He described it as “fighting fire with fire”.

“The virus might infect a cell but it wouldn’t spread,” said harrich of his study, published in the latest edition of the journal human Gene Therapy.

“You would still be infected with hIV, it’s not a cure for the virus, but the virus would stay latent, it wouldn’t wakeup, so it wouldn’t develop into AIDS,” he added. “With a treatment like this, you would maintain a healthy immune system.”

A person with hIV is said to have AIDS when their count of CD4 immune system cells drops below 200 per microlitre of blood or they develop what is known as an AIDS-defining illness; any one of 22 opportunistic infections or cancers related to hIV.

The majority of people infected with hIV, if left untreated, may not progress to AIDS for 10-15 years or longer,

according to the UN. Antiretroviral treatments can prolong this further still.

The new Nullbasic gene therapy, if proven, could see the deterioration from HIV to AIDS halted indefinitely, bringing an end to the deadly condition.

harrich said the fact that a single protein could be so effective could spell an end to onerous multiple drug regimes for hIV patients, meaning better quality of life and lower costs to individuals and governments.

“In that respect, this is a world-first agent that’s able to stop hIV with a single agent at multiple steps of the virus lifecycle,” harrich told ABC Radio.

“You either have to eliminate the virus infection or alternatively you have to eliminate the disease process and that’s what this could do, potentially for a very long time.”

Animal trials of the protein are due to start this year, with any treatment using it likely to be some years away.

According to the latest UN figures, the number of people infected by hIV

AUSTRAUSTRALIAN RESEARChERS hAVE FoUND A METhoD To TURN-oFF REPLICATIoN PRoCESS oF ThE hIV, SToPPING ThE VIRUS IN ITS

TRACKS AND PREVENTING IT FRoM PRoGRESSING To AIDS

The new drug could help slash the 24,000 unnecessary and premature deaths from diabetes each year, doctors believe.

It is also expected to lead to huge savings for the National health Service

(NhS) in the UK. Eighty per cent of the 10 billion pounds a year spent on diabetes goes on treating avoidable complications.

Tresiba, developed by Novo Nordisk, was approved by the European Commission

in January.“Trials of the drug have shown

rates of night-time hypoglycaemia were reduced by about a quarter,” Cathy Moulton, a clinical adviser at Diabetes UK, said.


Maharash-tra formul-ates special policy for organic farmingBUSINESS LINE2 February 2013

To encourage organic farming in Maharashtra, the State Government has formulated a special policy for the sector. The policy has devised a roadmap for developing the whole value chain — from the farm gate to the consumer.

The policy has defined organic farming as an integrated method, which uses local natural resources for farming and which rejects the use of chemicals for cultivation. Such a farming method will help improve the quality of land and reduce air and water pollution.

In Maharashtra, about 200 lakh hectares is under cultivation. over the last 15 years, a number of farmers’ groups have been practising organic farming techniques. The total area under organic

farming is still small, but it is growing steadily due to remunerative prices of such farms products in the metropolitan area.

Agriculture Commiss ioner of Maharashtra Umakant Dangat told Business Line that the policy has set an aim of converting 10 per cent of the total farmland to organic farms, and 25 per cent of the farm lands to use some agronomic practices of organic farming. The policy has not set out any milestones, but in the next five years, it wants to get the maximum area covered under this framing method, he said.

CAPitAl ReQuiReDhe said for implementing organic

farming methods across the State, not much capital is required. The farmers need to be made aware of these methods, which their forefathers use to practice.

“In fact, by using organic farming methods, farmers can save money and not have to shell out for fertilisers and

pesticides. If they convert farm waste into manure, their cost of cultivation can also be controlled,” Dangat said.

The policy is aiming to develop organic food safety standards, which are in sync with international ones. Incentives would be given for industries setting up units for processing, packaging and temperature controlled warehouses for organic foods. It also wants to develop a marketing infrastructure for such products.

Agriculture expert Raosaheb Pujari said awareness among farmers has been on the rise. Farmers know that chemicals are harmful for crops for personal consumption are grown using organic methods, “But a farmer’s land is now conditioned to chemicals. The farmer cannot switch overnight to organic methods, because his farm yield will take a hit,” he said.

“Today, a higher price for organic products and marketing infrastructure is the need of the hour. only then, organic farming will be successful,” Pujari said.

worldwide rose to 34 million in 2011 from 33.5 million in 2010.

The vast majority (23.5 million) live in sub-Saharan Africa, with another 4.2 million in South and Southeast Asia.

There were 1.7 million deaths from

AIDS-related causes worldwide in 2011, 24 per cent fewer than in 2005 and nearly six per cent below the 2010 1evel.

New hIV infections have at least halved in 25 low and middle income countries ,many in hard-hit Africa, over

the past decade, with particular progress made towards protecting children from the deadly virus.

The UN said in November that achieving zero new infections in children was appearing increasingly possible.

BULLETINBiotech


GM tobacco plant can treat rabiesDECCAN hERALD4 February 2013

A genetically altered version of the tobacco plant may provide an inexpensive cure for the deadly rabies

virus to patients in developing countries, scientists say.

In a new research reported in the FASEB Journal, scientists produced a monoclonal antibody in transgenic tobacco plants that was shown to

neutralise the rabies virus.The new antibody works by

preventing the virus from attaching to nerve endings around the bite site and keeps the virus from travelling to the brain.

“Rabies continues to kill many thousands of people throughout the developing world every year and can also affect international travellers,” said Leonard Both, a researcher involved in the work from the hotung Molecular

Genome feat hope for chhole, pakora aficionadosThE TELEGRAPh28 January 2013

Indian crop scientists have sequenced the chickpea genome, a feat they say will help boost yields of the nation’s best- selling legume used inmyriad dishes, from chhole to those requiring besan such as pakoras and bondas . The chickpea sequencing effort, led by scientists in hyderabad with collaborators elsewhere in India and other countries, has identified an estimated 28,269 genes or about 90 per cent of the genes in this staple crop. Their paper on the chickpea sequence appeared today in the journal Nature Biotechnology . Scientists say the newly identified genes will help accelerate efforts to improve India’s chickpea yields, which, at only 850kg per hectare in contrast to Canada’s 1,600kg per hectare, are still much lower than what agricultural scientists believe can be achieved.

“ India is the world’s largest producer, largest consumer and largest importer of chickpeas,” said Rajeev Varshney, a plant biologist at the International Crops Research Institute for Semi- Arid Tropics, hyderabad, who led the genome sequencing consortium.

“ We don’t produce enough to meet the domestic demand; so increasing the yield is important for India,” Varshney told The Telegraph . Some of the newly identified genes appear to control functions such as seed nutrition, adaptation to stress from heat and drought, and disease resistance.

When scientists identify genes for specific traits, they can focus breeding efforts on those particular genes.

“ It narrows the playing field— we can use this molecular information to make breeding efforts more precise,” said Douglas Cook, professor of plant pathology at the University of California, Davis, who played a key role in planning the project, assembling the sequence and analysing data.

Scientists are, for example, close to identifying specific genes that control flowering time. “ This may allow breeders to rapidly adapt new varieties to changes in climate,” Cook told this newspaper.

“ Similarly, we hope to find genes involved in disease resistance to important pests.” The consortium sequenced a widely cultivated Canadian kabuli chickpea variety as a reference genome and then sequenced 90 other lines from 10 countries, including 19 varieties of

chickpea from India.While Indian researchers had in

the past contributed to international efforts to sequence the genomes of rice and tomato plants, the chickpea is the second genome- sequencing effort to be led by Indian crop scientists, after they sequenced the pigeon pea genome two years ago.

In India, the main chickpea varieties cultivated and consumed are the desi chickpea, also called the Bengal gram, and the kabuli chickpea or Garbanzo beans.

“ It’s protein- rich and a primary protein source for vegetarians in India,” Varshney said. But demand overshoots supply and India has had to import chickpeas from Australia, Canada and Ethiopia, he said.

The chickpea is the world’s second- most widely grown legume after the soybean, and is used in cuisines across the world: mashed into hummus in West Asia, spiced into a salad in Mexico, or garnished with spinach in North America.

In recent decades, Cook said, chickpea production has moved from northern to southern India, where heat and late- season drought limit yield. “ If future breeding efforts can address these two issues, along with disease resistance, then yields could increase significantly.” The sequencing effort involved 49 scientists from 23 institutions across 10 countries.

Several institutions under the Indian Council of Agricultural Research, including the Indian Institute of Pulses Research, Kanpur, contributed to the sequencing effort.


Immunology Unit at St George’s, University of London, in the UK.

“An untreated rabies infection is nearly 100 per cent fatal and is usually seen as a death sentence. Producing an inexpensive antibody in transgenic plants opens the prospect of adequate rabies prevention for low-income families in developing countries,” Both said in a statement.

Both and colleagues “humanised” the sequences for the antibody so

people could tolerate it. Then, the antibody was produced using transgenic tobacco plants as an inexpensive production platform.

The antibody was purified from the plant leaves and characterised with regards to its protein and sugar composition. The antibody was also shown to be active in neutralising a broad panel of rabies viruses, and the exact antibody docking site on the viral envelope was identified using certain chimeric rabies viruses.

“Although treatable by antibodies if caught in time, rabies is bad news,” said Gerald Weissmann, Editor-in-Chief of the FASEB Journal.

“This is especially true for people in the developing world where manufacturing costs lead to treatment shortages. Being able to grow safe, humanised antibodies in genetically modified tobacco should reduce costs to make treatments more accessible, and save more lives,” Weissmann said.

Golden age of GM crops

hINDUSTAN TIMES12 February, 2013

Scientists say they have seen the future of genetically modified foods and have concluded that it is orange or, more precisely golden. In a few months, golden rice — normal rice that has been genetically modified to provide vitamin A to counter blindness and other diseases in children in the developing world — will be given to farmers in the Philippines for planting in paddy fields.

Thirty years after scientists first revealed they had created the world’s first GM crop, hopes that their potential to ease global malnutrition problems may be realised at last. Bangladesh and Indonesia have indicated they are ready to accept golden rice in the wake of the Philippines’ decision, and other nations, including India, have also said that they are considering planting it.

“Vitamin A deficiency is deadly,” said Adrian Dubock, a member of the Golden Rice project. “It affects children’s immune systems and kills around two million every year in developing countries. It is also a major cause of blindness in the third world. Boosting levels of vitamin A in rice provides a simple, straight-forward way to put that right.”

Recent tests have revealed that a substantial amount of vitamin A can be obtained by eating only 60g of cooked golden rice. “This has enormous potential,” said Dubock.

But scientists’ satisfaction over the Golden Rice project has been tempered by the fact that it has taken an extraordinarily longtime for the GM crop to be approved. Golden rice was first developed in 1999, but its development and cultivation has been opposed vehemently by campaigners who have flatly refused to accept that it could deliver enough vitamin A, and who have also argued the crop’s introduction in the developing world would make Farmers increasingly dependent on western industry. The crop has become the cause of the anti-GM movement, which sees golden rice as a tool of global capitalism.

This view is rejected by the scientists involved. “We have developed this in conjunction with organisations such as the Bill and Melinda Gates Foundation as a way of alleviating a real health problem in the developing world,” says Dubock. “No one is going to make money out of it. The companies involved in developing some of the technologies have waived their licences

just to get this off the ground.This view is shared by Mark Lynas, an

environmental campaigner and one of the founders of the anti-GM crop movement. he has publicly apologized for opposing the planting of GM crops in Britain. “The first generation of GM crops was suspect, I believed then, but the case for continued opposition to new generations — which provide life-saving vitamins for starving people — is no longer justifiable. You cannot call yourself a humanitarian and be opposed to GM crops today.”

“All the time, opponents to golden rice insisted, year after year, that it would not be able to produce vitamin A in those who ate it,” said Peter Beyer, golden rice’s co-creator. “For example, it was alleged by Greenpeace that people would have to eat several kilograms of the stuff to get any benefit.”

Two studies, both published in the American -Journal of Clinical Nutrition, demolished this claim. The first, in 2009, was based on a group of healthy adult volunteers in the US and showed that golden rice’s beta-carotene was easily taken up into the bloodstream.

The second trial was carried out by American and Chinese researchers and published last year. It was carried out on Chinese children, aged between six and eight, and showed that a bowl of cooked golden rice, between l00g and 150g, could provide 60% of the recommended intake of vitamin A for young people.

The fate of golden rice is therefore important, as professor Jonathan Jones of the John Innes Centre points out. “When I started making GM plants 30 years ago,

NEW AGE GoLDEN RICE, A NEW STRAIN ThAT BooSTS VITAMIN A LEVELS AND REDUCES BLINDNESS, IS ABoUT To BE SoWN IN ThE

PhILIPPINES

BULLETINBiotech


I did wonder if there might be unknown unknowns. But the evidence now is clear. GM food and crops are as safe as non-GM food and crops.”

The Golden Rice project has had one beneficial knock-on effect, however. It has triggered a series of similar crop modification programmes that aim to tackle vitamin A deficiency through use of other GM foodstuffs. one example is provided by the golden banana, which has been created by scientists led by professor James Dale of Queensland

University in Australia.“In Uganda, where the banana is a key

source of nutrition, there is considerable vitamin A defi-ciency and also iron deficiency in diets,” he said. “The former not only causes blindness but leaves children less able to fight disease which, in Africa, is particularly serious. The latter, iron deficiency, causes blood disoiders.”

To put this right, Dale and his team have found ways to boost beta-carotene levels in bananas. Now they are working

on boosting iron levels as well. The team expects to have developed a golden banana, that will raise both iron and vitamin A levels, by the end of the decade.

The result of the team’s work will be similar to golden rice: peeled, the pale fruit will be carrot-coloured. And if that sounds strange, it is worth noting that carrots were not originally orange. In the 17th century they were mostly yellow or purple, but were bred to be orange by dutch farmers in tribute to the ruling house of orange.

GolDen RiCe thRouGh the yeARS

BuReAuCRAtiC huRDleS

• Developers have described the reactions of bureaucracies, apart from those of the activist groups, as “hard to believe”

• “We have had to undergo endless trials and tests and endure endless amounts of bureaucracy. Yet new breeds of standard crops have no problems,” said Beyer

• Adrian Dubock, member of the Golden Rice project, said: “All the time we have been required to show that there are no risks associated with growing golden rice, but at no point did we get a chance to point out its benefits. Everything is about risk assessment and nothing is about benefits assessment.”

MAJoR ContRoVeRSy

• Opponents to golden rice have insisted that people would have to eat several kilograms of golden rice to get any benefit

• Two studies, published in the American Journal of Clinical Nutrition, demolished this claim

• However, one of the two studies, carried out on Chinese children, has been immersed in con troversy after it was claimed in a Greenpeace press release that the parents of the Chinese children had not been informed they were being given GM food and had been used as guinea pigs

• An investigation by the Chinese authorities led to the sacking of the three Chinese scientists named by Greenpeace.

• Golden rice was created by Peter Beyer, professor for cell biology at Freiburg University in Germany, and Ingo Potrykus of the Institute of Plant Sciences in Switzerland, in the late 1990s

• They inserted genes for a chemical known as beta-carotene into the DI\!A of normal rice In this way, they modified the rice genes so that the plants started to make beta-carotene, a rich orange-coloured pigment that is also a key precursor chemical used by the body to make vitamin A

A look at the development of the rice variety and the controversies surrounding it over the years

• By 2000, the plant was ready for trials

• However, it took another five years before test fields were grown, such was the resistance by activist groups to the idea of introducing GM plants in many countries

• These trials showed golden rice could stimulate vitamin A uptake but at a low level

• New research was launched to create varieties that would provide enhanced amounts of the vitamins to achieve the goal of the GM rice


Rice, a silver bullet to fight off cancer?

MUMBAI MIRRoR16 January, 2013

Juice from rice cells knocked out two kinds of human cancer cells as well or better than the potent anti-cancer drug Taxol in lab tests conducted by a Michigan Technological University scientist. Plus, it did something extra: it played nice with normal cells.

Biologist Ramakrishna Wusirika and his team made their anti-cancer cocktail with blobs of rice stem-cells called calli, which they cultured in their lab using seeds of the garden-variety rice plant oryza sativa.

Then they collected secretions from these calli and applied them to colon and kidney cancer cells in the lab. After 96 hours of exposure to a 20-to-l rice callus solution, 95 per cent of the kidney

cancer cells were killed, along with 83 per cent of the colon cancer cells, while normal lung cells were virtually unharmed.

While, Taxol was as lethal to the cancer cells, it also killed a significant number of normal cells. Wusirika thinks the rice callus culture may be attacking cancer with the same sort of plant chemicals that make vegetables so healthy to eat.

“They are full of metabolic com-pounds that are good for us,” he says. “We think that’s what is killing the cancer.”

Next, Wusirika would like to try the rice callus solution on prostate, lung and breast cancer cells, the most common types of cancer.

“We think it will work with all of them, but we need to find out,” he said.

he also wants to determine which of the compounds released by the rice callus have cancer-killing properties and how they work against tumour cells. or, he notes, it’s possible that the suite of biochemicals found in the callus solution work as a team to fight cancer.

Wusirika’s work is described in the article Anticancer Activity of Rice Callus Suspension Culture, published in the Phytotherapy Research journal.

A CoCKTAIL MADE oF RICE CELLS CAN KILL oFF CANCERoUS CELLS WhILE LEAVING NoRMAL oNES ALoNE

Scientists discover genetic key to more efficient crops


Scientists have discovered a new gene that could lead to new varieties of staple crops with 50 per cent higher yields, which they say could quell hunger in many countries.

The gene discovered by Cornell

University researchers could quell the ever growing challenge of feeding more humans, whose numbers are likely to bloat to 9.5 billion by 2050, with the same amount of water, fertilisers and arable land available today, scientists say.

Called Scarecrow, the gene is the first discovered to control a special leaf

structure, known as Kranz anatomy, which leads to more efficient photosynthesis.

Plants photosynthesise using one of two methods C3, a less efficient, ancient method found in most plants, including wheat and rice; and C4, a more efficient adaptation employed by grasses, maize, sorghum and sugarcane that is better suited to drought, intense sunlight, heat and low nitrogen.

Researchers have been trying to find the underlying genetics of Kranz anatomy so we can engineer it into C3 crops, said Thomas Slewinski, lead researcher of the study published in the journal Plant and Cell Physiology.

The finding provides a clue as to how this whole anatomical key is regulated, Turgeon said in a statement.

There’s still a lot to be learned, but now the barn door is open and you are going to see people working on this

ThE GENE DISCoVERED BY CoRNELL UNIVERSITY RESEARChERS CoULD QUELL ThE EVER GRoWING ChALLENGE oF FEEDING MoRE

hUMANS

BULLETINBiotech


Scarecrow pathway.The promise of transferring C4

mechanisms into C3 plants has been fervently pursued and funded on a global scale for decades, he added. If C4 photosynthesis is successfully transferred

to C3 plants through genetic engineering, farmers could grow wheat and rice in hotter, dryer environments with less fertiliser, while possibly increasing yields by half, the researchers said.

The C3 photosynthesis originated

at a time in Earth’s history when the atmosphere had a high proportion of carbon dioxide. C4 plants have independently evolved from C3 plants some 60 times at different times and places.

Fish stem cells may restore hu-man visionThE INDIAN EXPRESS2 February, 2013

Zebrafish, often used in genetics studies, may hold the key to repairing damaged retinas and returning eyesight to people, Canadian researchers say.

University of Alberta researchers discovered that a zebrafish’s stem cells can selectively regenerate damaged photoreceptor cells.

According to lead researcher Ted Allison, geneticists have known for some time that stem cells in zebrafish - unlike those in humans - can replace damaged cells involved in many components of eyesight.

Rods and cones are the most important photoreceptors. In humans, rods provide us with night vision and cones give us a full-colour look at the

world during the day. What was not known, says Allison, was whether the zebrafish stem cells could be instructed to replace only the cones in its retina. This could have important implications for human eyesight.

“This is the first time in an animal research model that stem cells have only repaired damaged cones,” Allison said in a statement.

“For people with damaged eyesight, repairing the cones is most important because it would restore daytime colour vision,” he said. The researchers say that to date, almost all success in regenerating photoreceptor cells has been limited to rods, not cones. Most of these previous experiments were conducted on nocturnal rodents,

animals that require good night vision and consequently have far more rods than cones.

“This shows us that when cones die in a cone-rich retina, it is primarily cones that regenerate. This suggests the tissue environment provides cues to instruct stem cells how to react,” said Allison.

The researchers say this shows hope for stem-cell therapy that could regenerate damaged cones in people, especially in the cone-rich regions of the retina that provide daytime colour vision.

“The next step for our team is to identify the particular zebrafish gene that activates repair of damaged cones,” said Allison. The study was published in the journal PLoS oNE.

New TB drug ready for clinical trialThE INDIAN EXPRESS2 February 2013

A new candidate drug against tuberculosis is all set to be tried on

drug-resistant TB patients in India with the hope that it would end a 50 year search for a new medicine against the disease that kills 1000 Indians daily.

Almost all TB drugs currently in use

were developed in the 1950s and 1960s. The last one was rifampicin in 1966. Isoniazid and pyrazinamide came in 1952 and ethambutol in 1961.

“In the last half a century, there were combinations but no new molecule. Recently one molecule (from a large pharmaceutical company) received US Food and Drug Administration’s approval for critical patients. But it is yet to complete the phase-III trial,” said


Geeta Vani Rayasam, a senior researcher in the Council of Scientific and Industrial Research.

Scientists are firming up their plans to start a Phase-II B clinical trial of the molecule – Pa824 – following encouraging Phase-I trials that assessed the drug’s safety.

The clinical trial is being spearhea-ded by the open Source Drug Discovery team of Council of Scientific and Industrial Research that has taken up the challenge of de-risking the high-cost drug development process in the absence of pharmaceutical industry’s lack of interest on TB drugs. “We will

seek the Drugs Controller General of India approval by March. The trial will be held in LRS Institute of Tuberculosis and Respiratory Diseases in Delhi involving 250-300 multi drug resistant TB patients,” Zakir Thomas, who heads the oSDD programme told Deccan herald.

This will be the first clinical trial of a TB drug in India by a public-funded organisation. In the past National Institute for Research on Tuberculosis in Chennai carried out India leg of a clinical trial for a molecule developed by a multinational firm. On the contrary Pa824 was synthesised in India decades

ago. After a series of ownership changes, the molecule was licensed to CSIR for further development and clinical trial by an international non-governmental organisation known as TB Alliance.

As many as 8 phase-I trials were conducted in the USA and South Africa in the last 5 years. The drug candidate was found to be safe expect in higher dose.

Two phase-II trials were conducted in Brazil and South Africa with promising results.

The Indian trial will have three arms, each involving 60-100 patients.

IISc scientists discover new molecule for cancer cureThE FINANCIAL EXPRESS7 January 2013

Scientists at the Indian Institute of Science (IISc) have discovered anew molecule that, they say, could potentially lead to an anti-cancer drug, which may help reduce the dosage of current treatment methods like chemotherapy or radiotherapy. The molecule, aimed at kill ing cancer cells by blocking their DNA repair mechanism, was successful in removing tumours in mice during laboratory experiments, say the researchers.

The team is now evaluating offers to collaborate, including one from a US-based pharma company, for further research and clinical trials. Typically, the road to market for a new molecule can take at least a decade.

The molecule named SCR7, developed chemically using bioinformatics tools, was found to be effective in the case of carcinoma, the most common form

of cancer in humans, but did not have any impact on leukemia or lymphoma, says Sathees Raghavan, associate professor at IISc’s department of Biochemistry. The paper’s first author Mrinal Srivastava is a PhD student at Raghavan’s laboratory and researchers from institutions, such as the KLE University College of Pharmacy and Institute of Bioinformatics and Applied Biotechnology (IBAB) in Bangalore and the Mumbai-based Advanced Centre for Treatment, Research and Education in Cancer (Actrec), also contributed to the study.

Cell damage in mammals such as a break in the double stranded DNA evokes two types of natural repair processes called homologous recombination and Non-homologous End Joining (NhEJ). The latter is a more widespread method of repairing double strand breaks in which the DNA uses a protein called Ligase IV to bind the strand. A break in the DNA double

exPeRtSPeAKSAThEES RAGhAVANassociate professor department of Biochemistry, IISc.T h e b e s t part of our finding is. ifit is successful in trials, it can improve r a d i o a ndehemo therapy which is generally used all over the world. Who knows, mavbe our molecule can bring down the dose of rad iation and that will have a lot of advantages with respect to patients

RitA MulheRKAR, scientist, Advanced Center for Treatment, Research and Education in CancerIt looks very pro-mis ing and it will be quite exciting if it can go

BULLETINBiotech


CRuCiAl BReAK thRouGh

• The new molecule, discovered by IISc scientists, is aimed at killing cancer cells by blocking their DNA repair mechanism

• It could potentially help reduce dosage of current chemotherapy and radiotherapy methods

• In India, an estimated 5,55 000 people died of cancer in 2010, according to a study

• Globally, cancer accounted for an estimated 7.6 Million deaths in 2008

strand can be a lethal form of damage and could lead to a tumour if it is not properly repaired.

“We have designed an inhibitor that can bind to the protein that is responsible for NhEJ repair, The idea here is if you can block the DNA repair specifically in cancer cells, that will result in the accumulation of DNA damage in these cells and kill that cell,” said Raghavan. “We are targeting this inhibitor on to Ligase IV so that the protein cannot bind to the DNA for repair.

Following the tests on cancer cells, the team studied four different tumour models in mice.

“What we found was that out of the four cases, three showed very good effect. 11 resulted in the regression of the tumour in a time dependent manner and about 3-4 fold increase in the lifespan of the mice,” said Raghavan.

Without treatment, the mice would have died in 45-55 days, but treating the tumours with the inhibitor molecule helped at least 50% of them live more than 350 days without side-effects, the study said. “The best part of our finding is, if it is successful in trials, it can improve radio and chemotherapy, which is generally used all over the world. Who knows, maybe our molecule can bring down the dose of radiation and that will have a lot of advantages with respect to patients,” added Raghavan. Typically, ionizing radiation and several chemotherapeut ic agents induce DNA breaks to cause cell death and Raghavan’s lab found that SCR7, when co-administered with the radiation or chemo-therapeutic agents, potentiated their effects many fold.

In India, an estimated 5,55,000 people died of cancer in 2010, according to a study by the Centre for Global health Research in Toronto along with the International Agency for Research on Cancer (IARC), an arm of the World health organisation, Globally, cancer accounted for 7.6 mil lion deaths in 2008, or around 13% of all deaths that year. An August 2012 factsheet of the IARC projected that the burden of

The molecule, aimed at killing cancer cells by blocking their DNA repair mechanism, was successful in removing tumours in mice during laboratory experiments, say the researchers.

cancer will likely increase to 22 million new cases each year by 2030, going by the recent trends in major cancers,

While cancer research globally looks at different approaches to killing cancer cells, the IISc study is among the few to demonstrate the role of a DNA repair inhibitor, says experts,

“It looks very promising and it will be quite exciting if it can go to clinical trials. But they still have to do a lot of biological studies to understand what is happening in the animal models,” says Rita Mulherkar, scientist at Actrec. A key area of the global research into cancer cure is kinase inhibitors, which target the enzyme involved in the cell proliferation pathway, she added. “It is the first approach which actual ly validates this concept in non-homologous end joining. The beauty of this paper is that they have shown that shutting down an enzyme can actually become a handle in the fight against cancer,” says Sagar Sengupta, a scientist at the Delhi-based National Institute of Immunology.

Raghavan says that the discovery of the molecule opens up several lines of study and can perhaps even lead to a better molecule. “obviously, we are

to clinical trials. But they still have to do a lot of biological studies to understand what is happening in the animal models

going to look in different directions to see how we can take this to the next level,” he says.

StAtfACtS


Modified virus kills liver cancer cells

MUMBAI MIRRoR12 February 2013

A genetically engineered virus tested in 30 terminally-ill liver cancer patients significantly prolonged their lives, killing tumours and inhibiting the growth of new ones, scientists reported. Sixteen patients

given a high dose of the therapy survived for 14.1 months on average, compared to 6.7 months for the 14 who got the low dose.

“For the first time in medical history we have shown that a genetically engineered virus can improve survival of cancer patients,” said study co-author

David Kirn.The four-week trial with the vaccine

Pexa-Vec or JX-594, reported in the journal Nature Medicine, may hold promise for the treatment of advanced solid tumours.

“Desp i te advances in cancer treatment over the past 30 years with chemotherapy and biologics, the majority of solid tumours remain incurable once they are metastatic (have spread to other organs),” the authors wrote. There was a need for the development of “more potent active immunotherapies.”

Pexa-Vec “is designed to multiply in and subsequently destroy cancer cells, while at the same time making the patients’ own immune defense system attack cancer cells also,” said Kirn from

RESEARChERS hAVE CREATED A VIRUS ThAT CAN INFECT AND KILL CANCERoUS CELLS WhILE REDUCING ThE SIZE oF ThE TUMoUR. DIE

oNLY SIDE-EFFECTS ARE FLU-LIKE SYMPToMS ThAT LAST A DAY oR TWo

Bacteria that can cure!DECCAN hERALD15 February 2013

Adiscovery about the way in which bugs spread throughout the bory could help to develop stem cell treatments.

Researchers at the University of Edin-burgh have found that bacteria are able to change the make-up of supporting cells within the nerve system, called Schwann cells, so that they take on the properties of stem cells.

Since stem cells can develop into any of the different cell types in the body mim-icking this process could aid research into a range of degenerative conditions.

Scientists made the discovery studying bacteria that cause leprosy, which is an in-fectious neurodegenerative disease. The study, carried out on mice, found that in the early stages of infection, the bacteria were able to protect themselves from the body’s immune system by hiding in the Schwann cells.once the infection was fully established, the bacteria were able to con-vert the Schwann cells to become like stem cells. Like typical stem cells, these cells could then become other

cell types, for in-stance muscle cells.This enabled the bacteria to spread

to tissues in the body. The bacteria-generated stem cells can secrete specialised proteins - called chemokines - that attract immune cells, which in turn pick up the bacteria and spread the infection. Scientists believe these mechanisms, used by leprosy bacteria, could exist in other infectious diseases.

Knowledge of this newly discovered tac-tic used by bacteria to spread infection could help research to improve treatments and earlier diagnosis of infectious dis-eases.The study is published in the journal Cell.

Professor Anura Rambukkana, of the Medical Research Council (MRC) Centre for Regenerative Medicine at the University of Edinburgh, who led the research, said: “Bacterial infections can completely change a cell’s make up, which could have a wide-range of implications, including in stem cell research.”The study, was funded by the US National Institutes of health.

fAtAl infeCtionIt showed that when an infected

Schwann cell was reprogrammed to become like a stem cell, it lost the function of Schwann cells to protect nerve cells, which transmit signals to the brain.

Professor Rambukkana added: “This is very intriguing as it is the first time that we have seen that functional adult tissue cells can be reprogrammed into stem cells by natural bacterial infection, which also does not carry the risk of creating tumorous cells. “Potentially you could use the bacteria to change the flexibility of cells, turning them into stem cells and then use the standard antibiotics to kill die bacteria completely so that the cells could then be transplanted safely to tissue that has been damaged by degenerative disease,” he added.

This discovery is important not just for our understanding and treatment of bac-terial disease, but for the rapidly progressing field of regenerative medicine.

v once the infection was fully established, the bacteria were able to convert the schwann cells to become like stem cells.

BULLETINBiotech


the biotherapy company Jennerex.“The results demonstrated that Pexa-

Vec at both doses resulted in a reduction of tumour size and decreased blood flow to tumours,” said a Jennerex statement. “The data further demonstrates that Pexa-Vec treatment induced an immune response against the tumour.”

Pexa-Vec has been engineered from the vaccinia virus, which has been used as a vaccine for decades, including in the eradication of smallpox. The trial showed Pexa-Vec to be well tolerated, with flulike symptoms lasting a day or two in all patients and severe nausea and vomiting in one.

The author said a larger trial has to

confirm the results. A follow up phase of about 120 patients is already underway.

Pexa-Vec is also being tested in other types of cancer tumour.

Cells with promiseDECCAN hERALD19 February 2013

Medical research Scientists from the Universit ies of Southampton and Edinburgh are now using stem cells and a new lightweight plastic to create artificial bone. Also, scientists from heriot-Watt University have developed a specialised 3D printing process using human stem cells. This could pave the way to purpose-built replacement organs for patients, eliminating the need for organ donation.

Artificial bone, created using stem cells and a new light weight plastic, could soon be used to heal shattered limbs. The use of bone stem cells, combined with a degradable rigid material that inserts into broken bones and encourages real bone to re-grow, has been developed at the Universities of Edinburgh and Southampton,

Researchers have developed the material with a honeycomb scaffold structure that allows blood to flow through it, enabling stem cells from die patient’s bone marrow to attach to the material and grow new bone. over time, the plastic slowly degrades as the implant is replaced by newly grown bone.

Scientists developed the material by

blending three types of plastics. They used a pioneering technique to blend and test hundreds of combinations of plastics, to identify a blend that was robust, light-weight, and able to support bone stem cells.

Successful results have been shown in the lab and in animal testing with the

focus now moving towards human clinical evaluation.

This new discovery is the result of a seven-year partnership between the University of Southampton and the University of Edinburgh. Ricliard oreffo, Professor of Musculoskeletal Science at the University of Southampton, comments. “Fractures and bone loss due to trauma or disease area significant clinical and socioeconomic problem. This


collaboration between chemistry and medicine has identified unique candidate materials that support human bone stem cell growth and allow bone formation. our collaborative strategy offers signif-icant therapeutic implications”

Professor Mark Bradlev, of the University of Edinburgh’s School of Chemistry, adds. “We were able to make and look at hundreds of candidate materials and rapidly whittle these down to one which is strong enough to replace bone and is also a suitable surface upon which to grow new bone. “We are confident that this material could soon be helping to improve the quality of life for patients with severe bone injuries, and will help maintain the health of an ageing population”

PRintinG PRoCeSSA specialised 3D printing process,

using human stem cells, could pave the way to purpose-built replacement organs for patients, eliminating the need for organ donation, immune suppression and the problem of transplant rejection.

The process, developed at heriot-Watt University, in partnership with a stem cell firm, takes advantage of the fact that stem cells can now be grown in Laboratory conditions from established cell lines, could also speed up and improve the process of drug testing by growing three dimensional human tissues and structures for pharmaceuticals to be tested on

A range of human stem cell cultures can now be grown, generation after generation, in laboratory conditions. Those cultures developed from cells from areas like bone marrow or skin are hardier but less flexible than those developed from embryonic material. While 3D printing of the tougher cell cultures has been achieved before, the new valve-based technique developed by Will Shu and his colleagues at heriot-Watts Biomedical Micro-engineering group are the first to print the more delicate embryonic cell cultures, which have an ability to replicate indefinitely and differentiate into almost am cell type in die human body.

Shu said. “To the best of our knowledge, this is the first time that these cells have been 3D printed. The technique will allow us to create more accurate human tissue models which are essential to in vitro drug development and toxicity-testing. Since the majority of drug discovery is targeting human disease, it makes sense to use human tissues. “In the longer term, we envisage the technology being further developed to create viable 3D organs for medical implantation from a patient’s own cells, eliminating the need for organ donation, immune suppression and the problem of transplant rejection.”

Shu’s team is working with a stem cell technology company, which has a good track record of applying new technologies to human stem cel l systems and will take the lead in developing 3D stem cell printing for commercial uses. Initially this will be in the areas of novel drug-testing products but in the longer term there is the goal of growing purpose-built replacement organs.

biotech bulletin - bcil.nic.in · biotech bulletin is a bi-monthly publication ... cipla’s medpro...

Documents